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Biomedical subjects

G Vassal

Publications and source records attributed to G Vassal.

82 records · Page 5Linked to original sources
PubMed1989

Pharmacokinetics of high-dose busulfan in children.

The pharmacokinetics of high-dose busulfan given orally at 1 mg/kg every 6 h over 4 days (total dose, 16 mg/kg) in combined chemotherapy followed by autologous bone marrow transplantation was studied in 12 children with a mean age of 7 years (range, 4-14 years). Busulfan levels in biological fluids were measured by a gas chromatographic assay with mass fragmentographic detection, using a deuterated analogue as the internal standard. In a high-dose regimen, busulfan followed one-compartment model kinetics with zero-order absorption. A mean maximal concentration of 803 +/- 228 ng/ml was achieved at 92-255 min after dosing. The mean elimination half-life was 2.33 h, and the mean total clearance was 119 +/- 54 ml/min per m2, with an apparent distribution volume of 27.10 +/- 11.50 l/m2. A mean trough level of 370 ng/ml was found throughout the 4 days of the chemotherapy course. There were no significant variations in pharmacokinetic parameters measured after the first and last doses. Busulfan was monitored in the CSF of nine children at 3.25-7 h after the last dose and was detected in all patients, with a mean CSF-to-plasma concentration ratio of 0.95 (range, 0.5-1.4).

Adolescent↗
PubMed1989

Enhanced cutaneous radiation effects following high-dose busulfan therapy.

Fifteen patients received irradiation after combined chemotherapy with high-dose busulfan followed by autologous or allogeneic bone marrow transplantation. Of nine patients irradiated between day 30 and day 70 after their engraftment, seven developed an increased radiation response in the skin: four showed enhanced reactions during irradiation, and three had a total or severe definitive alopecia more than 16 months after CNS irradiation. Six patients were irradiated after day 70; they had either normal reactions or none at all within the cutaneous radiation portals. The possibility that busulfan might be a radiosensitizer is raised.

Busulfan↗
PubMed1988

Juvenile granulosa cell tumor of the ovary in children: a clinical study of 15 cases.

Juvenile granulosa cell tumor (JGCT) in children accounted for 12% of all ovarian tumors treated in the Institut Gustave-Roussy (IGR) Pediatric Department from 1967 to 1985. The median age of the 15 girls was 8 years 7 months (range, 22 months to 15 years 7 months). Precocious pseudopuberty was present in six of the seven girls under 8 years. Of the other seven girls, one developed virilization symptoms. Surgery was the first treatment in each case. According to the Wollner classification, there were six stage I, one stage II, six stage III (including four ruptured tumors), and one stage IV JGCT cases. One patient was not available for staging. An adjuvant treatment (five chemotherapy and one radiotherapy combined with chemotherapy) was administered to six patients. Eleven girls are alive and free of disease, with a median follow-up of 6 years (range, 2 to 18 years). Four girls relapsed 6 to 17 months after surgery and died. Two of these relapses occurred in bone. The prognosis for JGCT in children is favorable for the lower stages when treated with surgery, but the best treatment for extensive and recurrent disease has yet to be determined.

Adolescent↗
PubMed1988

[Prophylaxis of Gram-positive infections after bone marrow graft. Controlled study of the 6-day administration of vancomycin. Intermediate analysis of 60 patients].

We prospectively evaluated after randomization in 60 consecutive recipients of bone marrow transplantation the efficiency of a short administration of vancomycin (10 mg/kg I.V. q 6 H, day -5 to +1). Thirty-three patients were randomized as controls and 27 were designed to receive vancomycin. Both groups were similar in terms of age, diagnosis, status, allogeneic or autologous graft, in vitro marrow treatment or not. Eighteen patients (30%) experienced bacteremias: 15/18 bacteremias were due to Gram positive organisms, including 11 streptococci. These infections occurred with a similar frequency in both groups, the relatively low incidence of bacteremias in this study needs further evaluation in new patients to insure the prophylactic effects of a course of vancomycin in bone marrow transplant recipients.

Adolescent↗
PubMed1987

Differentiated thyroid carcinoma in childhood: long term follow-up of 72 patients.

Seventy-two children with differentiated thyroid cancer who were 16 years old or younger at the time of initial treatment were followed for a median time of 13 yr. Initially, 18% had lung metastases, and 74% had palpable lymph nodes. Capsular invasion was found in 67%, and histological lymph node involvement in 90%. The recurrent laryngeal nerve chain and the jugulo-carotid chain were involved with the same frequency (greater than 80%). The anterior superior mediastinum was involved only in patients with involvement of the recurrent laryngeal nerve chain. Forty-three patients had a complete remission after initial treatment. In patients without distant metastases for whom surgery was macroscopically incomplete, relapses occurred 5 times more frequently than in patients whose surgery was complete. Six patients died from thyroid carcinoma at ages ranging from 19-44 yr, 12-33 yr after initial treatment, and 1 died from intercurrent disease. Despite favorable long term survival (90.3% at 20 yr), the standardized mortality ratio was equal to 8.1. This study underlines the need for complete surgical treatment and compulsive follow-up, which should be continued throughout the patient's life, in order to detect and effectively treat relapses of thyroid cancer.

Adenocarcinoma↗
PubMed1987

Hyponatremia and renal sodium wasting in patients receiving cisplatinum.

Three children with malignant solid tumors developed hyponatremia with renal sodium wasting associated with other signs of tubular dysfunction, such as hypokalemia or hypomagnesemia, a few days after cis-diammine dichloroplatinum (CDDP) administration. The normalization of serum electrolyte disturbances was obtained with increased parenteral intakes in fluids and electrolytes, and renal sodium wasting stopped by itself a few days later.

Adolescent↗
PubMed1986

[Acute lymphoblastic leukemia in Burkitt cells: clinical, therapeutic and prognostic aspects].

This presentation reports on patients with 13 B - acute lymphoblastic leukemia (ALL), treated with intensive chemotherapy. To date 5 patients are alive, in complete remission (greater than 24 months), 4 of them had CNS disease at diagnosis; 7 patients relapsed, 2 to 4 months after complete remission, 6 of them having CNS relapse, isolated or with bone marrow involvement. The improvement in prognosis of B-ALL results from intensive chemotherapy, but the prognosis remains poor because of early relapses, especially CNS relapses (survival rate is less than 50%). The authors propose new therapeutic approaches.

Adolescent↗
PubMedDate not supplied

Pharmacologically-guided dose adjustment of busulfan in high-dose chemotherapy regimens: rationale and pitfalls (review).

High-dose busulfan is used in conditioning regimens before allogeneic or autologous bone marrow transplantation (BMT) in adults and children. During the last six years, several studies have established the wide inter- and intrapatient variability of high-dose busulfan disposition. Clearance rate ranges from 0.8 to 20 ml/min/kg. Some factors of variability have been identified: age, alteration in hepatic functions, disease, circadian rhythmicity, drug interactions. Using a fixed dose of busulfan, wide interpatient variability in systemic exposure is thus expected, with eventual consequences on toxicity and efficacy. In adults, a pharmacodynamic relationship between a high busulfan systemic exposure and the occurrence of hepatic veno-occlusive disease (HVOD) has been established. A prospective controlled study demonstrated that busulfan dose-adjustment decreased the morbidity and mortality of HVOD in adults. So far, pharmacodynamic studies in children have failed to establish a toxic level. The present paper analyses the rationale for busulfan dose adjustment, and focuses on the eventual pitfalls that may jeopardize its reliability (drug absorption, chronopharmacology, drug interaction within the conditioning regimen, complex pathophysiology of HVOD). Further pharmacodynamic studies are required to establish a minimum therapeutic threshold in systemic exposure for bone marrow engraftment, especially in children undergoing HLA-compatible or incompatible allogeneic BMT for non malignant disease. The definition of a therapeutic window according to the disease and the type of BMT, along with the development of iv-busulfan, will allow accurate and effective pharmacologically-guided dose adjustment of high-dose busulfan. By the end of the century, busulfan plasma level monitoring and dose adjustment at the individual level may improve the outcome of patients undergoing BMT.

Administration, Oral↗